c-2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-r-5-ylmethyl]-acetamide | 343304-89-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: c-2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-r-5-ylmethyl]-acetamide
• CAS: 343304-89-2
• 化学式: C₂₂H₂₀F₄N₄O₃
• 分子量: 464.419
• InChiKey: NNQMIHBTQOXWRL-TYKWCNGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  89.13
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  c-2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-r-5-ylmethyl]-acetamide 在 水 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 26.0h， 生成 N-{2-[5-(4-Fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-5-methyl-[1,3]dioxan-5-ylmethyl}-2-phenyl-acetamide
  参考文献：
  名称：

  The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy

  摘要：

  RPR132331, a 2-(2-dioxanyl)imidazole. was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNF alpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00331-x
• 作为产物：
  描述：

  4-[2-(c/t-5-azidomethyl-5-methyl-[1,3]dioxan-r-2-yl)-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine 在 palladium on activated charcoal 甲酸铵 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 c-2,2,2-trifluoro-N-[5-methyl-2-{5-(4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl}-[1,3]dioxan-r-5-ylmethyl]-acetamide
  参考文献：
  名称：

  The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy

  摘要：

  RPR132331, a 2-(2-dioxanyl)imidazole. was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNF alpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00331-x